Our laboratory is continuing studies on structure function relationships of human hemoglobins. In particular, we will focus on two projects: 1. Molecular basis of sickling. The participation of non-S hemoglobins in the polymerization of Hb S will be studied by ultracentrifugation which will separate the sol and gel phases. We will also investigate the effect of specific chemical modifications on sickling. 2. Evaluation of new hemoglobin variants. Structural and functional studies will be done on a limited number of hemoglobin variants. In addition, we plan to evaluate the biosynthesis of selected variants by incubation of reticulocyte preparations. BIBLIOGRAPHIC REFERENCES: Jensen, Michael, Oski, Frank A., Nathan, David G., and Bunn, H. Franklin: Hemoglobin Syracuse (alpha2 beta2 143 (H21)His Pro), a New High-Affinity Variant Detected by Special Electrophoretic Methods. J. Clin. Invest. 55:469-477, 1975. Bunn, H. Franklin, Schmidt, Geoffrey J., Haney, David N., and Dluhy, Robert G.: Hemoglobin Cranston, an unstable variant having an elongated beta chain due to non-homologous crossover between two normal beta chain genes. Proc. Nat. Acad. Sci. 72:3609-3613, 1975.